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Treatment of myasthenia gravis

OfficialreprintfromUpToDate
www.uptodate.com2014UpToDate
Treatmentofmyastheniagravis
Author
ShawnJBird,MD

SectionEditors
JeremyMShefner,MD,PhD
IraNTargoff,MD

DeputyEditor
JohnFDashe,MD,PhD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Jul2014.|Thistopiclastupdated:Jul31,2013.
INTRODUCTIONMyastheniagravis(MG),onceauniformlydisablingandevenfataldisorder,canbemanaged
effectivelywithcurrenttherapeuticstrategies.Manypatientscanevenachievesustainedremission.The
therapeuticapproachhascertaingeneralprinciples,butitishighlyindividualizedforeachpatient.Itdependsupon
theageofthepatient,theseverityofthedisease,particularlydictatedbyrespiratoryorbulbarinvolvement,andthe
paceofprogression[14].
ThistopicwilldiscussthegeneraltreatmentofMG.Detailedreviewsofchronicimmunomodulatingtherapiesfor
MGandthymectomyforMGarefoundseparately.MyastheniccrisisandthetreatmentofocularMGandMGin
pregnancyarealsodiscussedingreaterdetailseparately.(See"Chronicimmunomodulatingtherapiesfor
myastheniagravis"and"Thymectomyformyastheniagravis"and"Managementofmyastheniagravisin
pregnancy"and"Ocularmyastheniagravis"and"Myastheniccrisis".)
OVERVIEWTherearefourbasictherapiesusedtotreatMG:
Symptomatictreatments(anticholinesteraseagents)
Chronicimmunomodulatingtreatments(glucocorticoidsandotherimmunosuppressivedrugs)
Rapidimmunomodulatingtreatments(plasmapheresisandintravenousimmuneglobulin)
Surgicaltreatment(thymectomy)
Symptomscanbetreatedwithacetylcholinesteraseinhibitors(alsocalledanticholinesterasemedications).These
medicationsareallthatiseverneededforsomepatients.Pyridostigminebromide(Mestinon)isthemain
cholinesteraseinhibitorcurrentlyinuse.(See'Symptomatictreatment'below.)
However,mostpatientswithMGrequiresomeformofimmunotherapyatsomepointintheirillness,ifnot
indefinitely.Evenwhenimmunotherapeuticdrugsareused,itiscommontocontinuetheuseofanticholinesterase
medicationsinordertoreducethedosageofimmunosuppressivedrugsandthereforeminimizetheiradverse
effects.BalancingtheimprovementofMGsymptomswiththesideeffectsoftheimmunotherapeuticagentsis
alwaysachallengefortheclinicianandpatient.
CommonlyusedimmunotherapeuticdrugsinMGareprednisone,azathioprine,cyclosporine,andmycophenolate
mofetil.Insomecircumstances,particularlyinthosewithrefractoryMG,otheragentssuchasrituximab,monthly
pulsecyclophosphamide,andtacrolimusmaybeconsidered.(See"Chronicimmunomodulatingtherapiesfor
myastheniagravis".)
Plasmapheresisandintravenousimmuneglobulin(IVIG)arerapidimmunotherapiesthatworkquicklybuthavea
shortdurationofaction.Theseareusuallyreservedforcertainsituations,suchasmyastheniccrisis,preoperatively
beforethymectomy,asa"bridge"whileinitiatingsloweractingimmunotherapies,orasanadjuvanttoother
immunotherapeuticmedicationsinpatientswithrefractoryMG.(See'Rapidimmunotherapies'below.)
Manyexpertsbelievethatthymectomyisbeneficialinthosepatientslessthanage60whohavegeneralizedMG
withoutthymoma,althoughtherearenoprospectiverandomized,blinded,controlledtrials[5].However,itgenerally
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takesyearsforthebenefitsofthymectomytoaccrue.(See"Thymectomyformyastheniagravis".)
ThetimeofonsetofclinicaleffectofeachofthesetherapiesforMGvariesconsiderably(table1).Thisplaysa
largerole,inadditiontothepaceandseverityofthedisease,inchoosingtheappropriatetherapyforagiven
patient.
SYMPTOMATICTREATMENTTheinitialtherapyformostpatientswithmyastheniagravis(MG)isanoral
anticholinesterase(ie,acetylcholinesteraseinhibitor)medication,usuallypyridostigminebromide.
Acetylcholinesteraseinhibitorsretardthedegradationofacetylcholine(ACh)thatoccursbyenzymatichydrolysisin
theneuromuscularjunction[6].Asaresult,theeffectofAChisprolonged,leadingtoavariableimprovementin
strength.
Acetylcholinesteraseinhibitorsprovidemarkedimprovementinsomepatientsandlittleornoneinothers.Oftenthe
symptomimprovementmaybemixed,withmarkedimprovementinsomesymptomsbutnotothers(forexample,
resolutionofneckweaknessandptosiswithpersistenceofdiplopia).Ingeneral,limbandbulbarsymptoms
(dysphagia,fatigablechewing,anddysarthria)respondbettertoanticholinesterasedrugsthantheocular
manifestations(ptosisanddiplopia).Diplopiaisparticularlyresistanttothesemedicationsinmanypatients[7].
Acetylcholinesteraseinhibitorsarethefirstlineoftreatmentduetotheirsafetyandeaseofuse.Pyridostigmine
(Mestinon)istheusualchoice.Neostigmineisavailablebutnotcommonlyused.Acetylcholinesteraseinhibitors
provideonlysymptomatictherapyandareusuallynotsufficientingeneralizedMG.Nonetheless,insomepatients
thisistheonlytherapyeverneededforgoodcontrol.
PyridostigminedosingPyridostigminehasarapidonsetofaction(15to30minutes)withpeakactionatabout
twohours,anditseffectslastforthreetofourhours,sometimeslonger.Despiteitsshortdurationofaction,some
patientscanuseitquiteeffectivelywithdoseseverysixhoursorthreetimeaday.Othersneedadoseeverythree
hourstomaintainsymptomaticbenefit.
Foradultsandolderadolescents,acommonstartingdoseispyridostigmine30mgthreetimesaday.The
doseisthentitratedbyitseffect.Themaximaldoseandfrequencyisusually120mgeveryfourhourswhile
awake.Anoccasionalpatientwillneedtotakeadoseeverythreehours,butneveratshorterintervals.
Almostalladultpatientsrequireatotaldailydoseof960mg,dividedintofourtoeightdoses.
Forchildrenandyoungeradolescents,theinitialdoseis0.5to1mg/kgeveryfourtosixhours[8,9],uptoa
totaldailydoseof7mg/kg.
Pyridostigmineisavailableasscored60mgtabletsandasaliquidformulation.Pyridostigmineisalsoavailablein
anintravenouspreparationandcanbegiveninpatientswhocannottakeoraldrugs.Thisisusuallyinthesettingof
myastheniccrisis.(See"Myastheniccrisis".)
Itshouldbekeptinmindthatnofixedpyridostigminedosingschedulefitsallpatients.Mostadultpatientswho
responddosointherangeof60to90mgeveryfourtosixhourswhileawake.Someadultsrequireasmuchas
120mgeverythreetofourhourswhileawake.Dosesabovethisarerarelybeneficialandareusuallylimitedbythe
bothersomecholinergicsideeffects(see'Sideeffects'below).Whenapatienthassignificantpersistentweakness
despitetheuseofpyridostigmineinsufficientdoses,orthesideeffectsprecludeeffectivedosing,then
immunotherapyisgenerallywarranted.
Thedoseregimenusedmustbethoughtfullyindividualizedtogetsymptomaticbenefitsandtolimitunnecessary
cholinergicsideeffects.Asanexample,manypatientsonlyhavesignificantsymptomsintheevening.Anadult
patientmightdowellwithnopyridostigmineuntilalunchtimedoseof60mgfollowedfourhoursandeighthours
laterby90mg.Thosewhohavetroublechewingormilddysphagiamightbenefitbytakingadose30minutes
beforeameal.Therearenumerouscombinationsthatworkbestforanindividualpatient,basedupontheseverity
ofsymptoms,theresponsetopyridostigmine,andtolerationofsideeffects.Medicationsthatalleviatesomeofthe
cholinergicsideeffectsofpyridostigminemayalsobehelpful(see'Alleviatingsideeffects'below).
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Alongactingformulationofpyridostigmine(MestinonTS,180mg)isalsoavailable.Itisusedasabedtimedosein
patientswithpersistent,severeweaknessuponawakening.Mostpatients,however,dobetterafteranight'ssleep,
andthosewithmildweaknessuponawakeningmaydoaswellbytakingastandardpyridostigminedoseatthat
time.Longactingpyridostigmineisnotagoodchoicefordaytimeusebecauseitsvariablereleaseanddelayed
absorptionmakeitdifficulttoprovideaconsistenteffectandtoregulatetheoverallpyridostigminedose.
SideeffectsAdverseeffectsofpyridostigminearemostlyduetothecholinergicpropertiesofthedrug.
Thesecholinergiceffectscanbedoselimitinginmanypatients.Themostbothersomemuscarinicsideeffects
includeabdominalcrampinganddiarrhea.Othersareincreasedsalivationandbronchialsecretions,nausea,
sweating,andbradycardia.Nicotinicsideeffectsarealsofrequentandincludefasciculationsandmusclecramping.
However,theseareusuallylessbothersomethanthegastrointestinaleffects.
AlleviatingsideeffectsTakingpyridostigminewithfoodcanhelptoreducebothersomegastrointestinalside
effects.Muscarinicsideeffectscanbecontrolledinmanypatientswiththeuseofanticholinergicdrugsthathave
littleornoeffectatthenicotinicreceptors(ie,donotproduceincreasedweakness).Theseincludethefollowing
agents:
Glycopyrrolate1mg
Propantheline15mg
Hyoscyaminesulfate0.125mg
Theseanticholinergicdrugscanbetakenprophylacticallythreetimesadayor,alternatively,witheach
pyridostigminedose.
Prominentdiarrheacanbereducedbytheadditionofloperamide(Imodium)ordiphenoxylatehydrochlorideatropine
sulfate(Lomotil)withorwithoutotheranticholinergicdrugs.
CholinergiccrisisApotentialmajorsideeffectofexcessiveanticholinesterasemedicationisweakness,which
canbedifficulttodistinguishfromworseningMG.Thisparadoxicalweakeningwithanticholinesterasemedications
iscalled"cholinergiccrisis."However,cholinergiccrisisisrarelyifeverseenwithdoselimitationofpyridostigmine
to120mgeverythreehours,oratotaldailydoseof960mg.Cholinergiccrisisissorarethatitshouldnotbethe
presumedcauseofincreasingweaknessunlessthedosestakenareknowntosignificantlyexceedthisrange.
Otherwise,eveninthepresenceofcholinergicsideeffects,itshouldbeassumedthatthepatient'sunderlyingMG
isworseningandappropriatetreatmentshouldbeinitiated.
Somehaveadvocatedtheuseoftheedrophonium(Tensilon)testtodetermineifthereistoomuchortoolittle
anticholinesteraseeffectinthissetting,butthishasnotprovedtobereliableandisnotrecommended.(See
"Diagnosisofmyastheniagravis",sectionon'Tensilontest'.)
CHRONICIMMUNOTHERAPIESThesecondtherapeuticmodalityinMGistheadministrationof
immunomodulatingagents.Glucocorticoidsarewidelyusedaswellasotheragents,mostcommonly,azathioprine,
mycophenolatemofetil,andcyclosporine.Theonsetofactionvariesconsiderably,andthisplaysaroleinthe
choiceoftherapy(table1).
Theadministrationofmoderateorhighdosesofglucocorticoidsleadstoremissioninabout30percentofpatients
andmarkedimprovementinanother50percent.Theonsetofbenefitgenerallybeginswithintwotothreeweeks.
However,atransientdeteriorationoccursinupto50percentofpatientswithMGwhenhighdoseglucocorticoids
arestarted,usuallyoccurring5to10daysaftertheinitiationandlastingaroundfiveorsixdays.Forthisreason,
glucocorticoidsaremostoftenstartedinhighdosesonlyinhospitalizedpatientswhoarereceivingconcurrent
plasmapheresisorintravenousimmuneglobulin(IVIG)formyastheniccrisis.(See"Myastheniccrisis".)
Toavoidthetransientworsening,anoutpatientglucocorticoiddoseescalationregimenworksquiteeffectively.
AdetaileddiscussionofglucocorticoidsandotherimmunomodulatingagentsforMGaswellasthedatasupporting
theiruseisfoundseparately.(See"Chronicimmunomodulatingtherapiesformyastheniagravis".)
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RAPIDIMMUNOTHERAPIESTherapidtherapiesusedinMGarealsoimmunomodulatingbutaredistinct
becauseoftheirquickonset,transientbenefit,andtheiruseinselectsituations.Bothplasmapheresisand
intravenousimmuneglobulin(IVIG)starttoworkquickly(overdays),butthebenefitsareonlyshortterm(weeks).
Thesetherapeuticmodalitiesareusedmostofteninthefollowingsituations:
Myastheniccrisis(see"Myastheniccrisis")
Preoperativelybeforethymectomyorothersurgery(see"Thymectomyformyastheniagravis")
Asa"bridge"tosloweractingimmunotherapies(see'Bridgetherapy'below)
PeriodicallytomaintainremissioninpatientswithMGthatisnotwellcontrolleddespitetheuseofchronic
immunomodulatingdrugs
PlasmapheresisPlasmapheresis(plasmaexchange)directlyremovesacetylcholinereceptor(AChR)antibodies
fromthecirculation.Clinicalimprovementwithplasmapheresisroughlycorrelateswiththereductioninantibody
levels,asillustratedbythefollowingreports[1012].
InfivepatientswithrefractoryMG(moderatetoseveredisabilitydespitetreatmentwiththymectomy,high
doseprednisoneandcholinesteraseinhibitors),plasmapheresiscombinedwithprednisoneandazathioprine
therapyproducedclinicalimprovement[10].SerialdeterminationsofserumAChRantibodytitersshoweda
declinetoameanof21percentofthebaselinelevelsconcurrentlywithimprovedstrength.Clinically
improvedpatientsmaintainedloweredAChRtiters,whereasclinicalrelapseswereassociatedwitharebound
inAChRtiters.
InsevenpatientswithacquiredMGwhohadelevatedserumAChRantibodytiterstherewasaninverse
associationbetweenimprovementofmusclestrengthandfallofantiAChRtiters[11].Therewasaminimum
timelagoftwodaysfortheclinicalresponsetoplasmapheresis.
Thebeneficialclinicaleffectofplasmapheresisisusuallyseenwithindays,butthebenefittypicallylastsonlythree
tosixweeks.Inaddition,theAChRantibodylevelsreboundwithinweeksifnoconcurrentimmunotherapy(eg,
glucocorticoids)isused.
Plasmapheresisisanestablishedtreatmentforseriouslyillpatientsinthemidstofmyastheniccrisis.The
evidencesupportingitsuseinthissituationisdiscussedseparately.(See"Myastheniccrisis",sectionon
'Plasmapheresis'.)
Plasmapheresisisnotausefullongtermtreatment,sincetheneedforrepeatedexchangesoftenleadstoproblems
withvenousaccess(see'Complications'below).
Apotentialinnovation,notwidelyadapted,istheuseofplasmapheresiswithanimmunosorbentcolumnconsisting
ofstaphylococcalproteinA[13].ThistechniquemoreefficientlyremovesIgG,theimmunoglobulinthatincludes
thoseagainstacetylcholinereceptorsinMG.
Inafurtherrefinement,aJapanesegrouphasdesignedanacetylcholinereceptorantibodyspecificimmunosorbent
columnusingapeptideisolatedfromtheacetylcholinereceptorofTorpedoCalifornica,calledMedisorbaMG.This
columnistargetedtoremovetheblockingacetylcholinereceptorantibody[14].Thistechniqueisapprovedforuse
inJapanwhereithasproducedclinicalimprovementin78percentofcases[15].Itspotentialadvantagesinclude
selectiveremovalofantiAChRantibodieswithoutremovingotherusefulimmunoglobulinsfromtheplasmaandno
requirementforalbuminreplacement.However,ithaslimitedclinicaluseandhasnotyetbeenshowntobe
superiortoplasmapheresiswithregardtoefficacy,cost,andsafety.
CourseoftreatmentAtypicalcourseoftreatmentconsistsoffiveexchanges(3to5Lofplasmaeach)over
7to14days.ThereplacementfluidisalbuminwhenusedinthetreatmentofMG.Althoughdonedailyinsome
circumstances,exchangesdoneeveryotherdayareprobablymoreeffectiveinreducingtheantibodylevelsdueto
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thetimeittakesfortheextravascularimmunoglobulintoreequilibrateaftereachplasmaexchange.(See
"Therapeuticplasmaexchange:Prescriptionandtechnique".)
ComplicationsRepeatedplasmapheresisinvariablyleadstoinadequateperipheralvenousaccessandthen
requiresplacementofalargebore,doublelumencentralcatheter(subclavianorinternaljugular).Significantchronic
cathetercomplicationscanresult,suchasinfectionandthrombosis.Inadditiontothecathetercomplications,
plasmapheresiscanalsoproduceotheradverseeffectsincludingbleeding,hypotension,cardiacarrhythmias,
musclecramps,andatoxicreactiontothecitrateusedintheprocedure[16].(See"Therapeuticplasmaexchange:
Complications".)
Despitetheseconcerns,plasmapheresiscanbeusedsafelyforpatientswithMG.Inananalysisof42patients
withmoderatetosevereMGwhoweretreatedwithplasmapheresisinaprospectivetrial,therewereno
complicationsin55percentandmildtomoderatecomplicationsthatdidnotrequirestoppingtreatmentin45
percent[17].Theadverseeventsinthisstudyweremainlycitratereactionsandperipheralvascularaccess
problemsthatwereeasilymanaged.Inmostcases,plasmapheresiswasperformedintheoutpatientsetting(90
percent)usingperipheralvenousaccess(83percent).
IntravenousimmuneglobulinIntravenousimmunoglobulin(IVIG)ispooledimmunoglobulinfromthousandsof
donors.ThemechanismofactionforIVIGinMGisuncertain.Aswithplasmapheresis,theeffectofIVIGisseen
typicallyinlessthanaweek,andthebenefitcanlastforthreetosixweeks.(See"Generalprinciplesintheuseof
immuneglobulin",sectionon'Mechanismsofaction'.)
IVIGisusedinthesamesettingasplasmapheresistoquicklyreverseanexacerbationofmyasthenia.Thelimited
evidencesupportingitsuseinthissituationisdiscussedseparately.(See"Myastheniccrisis",sectionon
'Intravenousimmuneglobulin'.)
IVIGalsooffersanalternativetoplasmapheresisormultipleimmunosuppressiveagentsinselectpatientswith
refractoryMG,asapreoperativetreatmentbeforethymectomy[18,19],orasa"bridge"tosloweracting
immunotherapies.
Aswithmyastheniccrisis,therearelimiteddataregardingtheeffectivenessofIVIGforMGwithoutcrisis[20,21].
Inadoubleblindtrial,51patientswithmildtomoderateMGandworseningweaknesswererandomly
assignedtoIVIG(2g/kggivenovertwodays)orplacebo(anequivalentvolumeofdextrose5percentin
water)[22].Exclusioncriteriaincludedrespiratorydistress,vitalcapacity<1liter,andsevereswallowing
difficulty.PatientstreatedwithIVIGshowedamodestbutstatisticallysignificantimprovementcompared
withplacebointheQuantitativeMyastheniaGravis(QMG)Scorefordiseaseseverityatday14.The
improvementpersistedbutfailedtoachievestatisticalsignificanceatday28.Insubgroupanalysis,IVIG
treatmentwasassociatedwithclinicallyandstatisticallysignificantimprovementinpatientswithmore
severediseaseatstudyonset(QMG>10.5),butnoimprovementwasobservedinpatientswithmilder
disease(QMG<10.5).
AdoubleblindrandomizedtrialcomparedtreatmentwithIVIGversusplasmapheresisfor81adultswithMG
andworseningweaknessrequiringchangeintherapy[23].Atbaseline,59percentofpatientshadmild
disease,40percenthadmoderatedisease,whileonly1percenthadseveredisease.Patientswhohada
flareproducingmoderatetoseveredisease(aQMGscore>10.5)weretreated.Atday14,asimilar
proportionofpatientsassignedtoIVIGandplasmapheresishadimproved(69versus65percent)andthe
durationofimprovementwasalsosimilarwithlongerfollowup.
Inearlierobservationalreports,IVIGwaseffectiveinnearly70to75percentofpatientswithMG[24,25].
DoseandsideeffectsThetotaldoseofIVIGis2g/kg,usuallyovertwotofivedays.Spreadingthedose
overmoredaysispreferableinthosewhohaverenaldisease,congestiveheartfailure,orareelderly.
ThesideeffectsofIVIG[26,27]aremostcommonlymildandarerelatedtotheinfusionrate.Theseinclude
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headache,chills,dizziness,andfluidretention.Otheruncommoncomplicationsincludeasepticmeningitis,acute
renalfailure,thromboticevents,andanaphylaxis.
Theacutenephrotoxicitythatoccursinsomepatientsappearstoberelatedtothehighsucrosecontentofsome
preparationsofIVIGtheriskisincreasedwithunderlyingrenalinsufficiency.Anaphylaxishasbeenassociated
withIgAdeficiencyhowever,itisrarelyseeninpatientstreatedforautoimmuneneuromusculardiseases[27].
ThromboticeventsassociatedwithIVIGuseincludemyocardialinfarction,stroke,andpulmonaryembolism.(See
"Generalprinciplesintheuseofimmuneglobulin"and"Immuneglobulintherapyinprimaryimmunodeficiency".)
THERAPEUTICAPPROACHTheabovediscussiondetailsthevariousoptionsinthetreatmentofthepatient
withMGalongwithcertaingeneralprinciplesthatcanactasaframeworkfortreatingpatients(see'Overview'
above).However,itshouldalwaysbekeptinmindthatthetreatmentofMGishighlyindividualizedforeach
patient.Treatmentchoicesdependontheageofthepatient,theseverityofthedisease,particularlythepresence
ofbulbarorrespiratorysymptoms,andthepaceofprogression.
Inaddition,specialcircumstancescandictatedifferentapproachestotreatMG.Thissectionwillreviewthe
approachinadultswithgeneralizedMGandocularMG,adultsover60yearsofage,andchildren.Thetreatmentof
MGinpregnancyandapproachtosevereMGexacerbationsincludingmyastheniccrisisismentionedbelowbutis
discussedingreaterdetailseparately.(See"Managementofmyastheniagravisinpregnancy"and"Myasthenic
crisis".)
GeneralizedmyastheniaTheinitialstepinmostadultpatientswithmildormoderatediseaseissymptomatic
therapyintheformofpyridostigminebromide(see'Symptomatictreatment'above).Thosewithseveredisease,or
rapidlyworseningdisease,shouldbetreatedmuchlikethoseinmyastheniccrisis(see"Myastheniccrisis")using
rapidtherapies(ie,intravenousimmunoglobulinorplasmapheresis)followedbylongeractingimmunotherapies(see
"Chronicimmunomodulatingtherapiesformyastheniagravis")suchasglucocorticoids,azathioprine,
mycophenolatemofetil,orcyclosporine.
Whenstartingpyridostigmineforanolderadolescentoradult,webeginat30mg(1/2tab)withmealsthreetimesa
dayfortwotothreedaystoassessthecholinergicsideeffects(see'Pyridostigminedosing'above).Forthosewith
excessivecholinergicsideeffectsweaddanagent(eg,glycopyrrolate1mgwitheachpyridostigminedose)to
blockthosebothersomesymptoms.Forthosewhotoleratethepyridostigminewell,withorwithoutanticholinergics,
weincreasethedoseby30mgincrementsuntilwegettoagoodtherapeuticeffectorarelimitedbysideeffects.
Themaximumdoseisusually120mgeveryfourhourswhileawake.Anoccasionalpatientmayneedtotakeit
everythreehourswhileawake.Forthosewithbothersomesymptomsuponawakeninginthemorning,weusea
longactingformofpyridostigmine(MestinonTS180mg)atbedtime.
Forchildrenandyoungeradolescents,theinitialdoseis0.5to1mg/kgeveryfourtosixhours(see'Pyridostigmine
dosing'above).Thiscanbetitratedupslowlybasedonthetherapeuticresponseandsideeffects.Themaximal
dailydoseis7mg/kgper24hoursdividedinfivetosixdoses.
Forthosepatientsonpyridostigminealonewhosesymptomsareundergoodcontrolorinremission,wesimply
followtheirclinicalcourse.Thymectomyshouldbeconsideredinalladultpatientsunderage60aswell(see
"Thymectomyformyastheniagravis").Althoughtherearesomepatientswhodowelllongtermonpyridostigmine
alone,mostpatientswithgeneralizedMGultimatelyrequiresomeformofimmunotherapy(see"Chronic
immunomodulatingtherapiesformyastheniagravis").
AdditionofimmunomodulatingagentAnimmunotherapeuticagentisusuallyrequiredforpatientswho
remainsignificantlysymptomaticonpyridostigmine,orwhobecomesymptomaticagainafteratemporaryresponse
topyridostigmine.Thechoiceofagentmostoftenprednisone,azathioprine,mycophenolate,orcyclosporine
dependsonmanyfactors.Theseincludetherelativecontraindicationstoglucocorticoids(suchasdiabetesor
advancedage),liverdisease(precludingazathioprineuse),renaldisease(precludescyclosporineuse),or
leukopenia(problematicforbothazathioprineandmycophenolate).Thedesiredtimeforresponseonsetalsoisa
factor(table1),varyingfromtwotothreeweekswithprednisoneto6to12monthswithazathioprine.Costis
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anotherimportantconsideration.(See"Chronicimmunomodulatingtherapiesformyastheniagravis".)
Inyoungadultpatients,particularlythoseofchildbearingpotential,wefavortheuseofglucocorticoids.Weoften
cangetagoodresponsewithhighdosesinitiallyandthenmaintainthatresponseafteraslowtaperdowntolow
doses(ontheorderof10mgdailyofprednisone).Wealsouseglucocorticoidsinolderindividualswhoneeda
relativelyquickresponsetoimmunotherapyandthentrytoaddanotheragent(mostoftenazathioprineor
mycophenolatemofetil)toreplacetheglucocorticoidsforthelongterm.
Thereareanumberofreasonableapproachestostartingprednisone,includingdailyandalternatedaydosing.
Dosingofglucocorticoids,includingdoseescalationandtapering,isdiscussedseparately.(See"Chronic
immunomodulatingtherapiesformyastheniagravis",sectionon'Glucocorticoids'.)
Forpatientswhocannotbetaperedtolowdoseswithoutclinicalrelapseorinthosepatientswherelongterm
prednisoneisnotdesirable,evenatlowdoses,anotherimmunomodulatingagentissubstituted.
Weaddaglucocorticoidsparingagent,orglucocorticoidreplacement,whenwearedowntothelowestdoseof
prednisonethatwillmaintainareasonableclinicalresponse.Effectiveglucocorticoidsparingagentsinclude
azathioprine,mycophenolatemofetil,andcyclosporine.(See"Chronicimmunomodulatingtherapiesformyasthenia
gravis",sectionon'Glucocorticoidsparingagents'.)
Aftertheminimumtimetoonsetofclinicalresponsefortheaddedimmunotherapy(eg,often12monthsormorefor
azathioprine)haspassed,wethenslowlytaperprednisonetoaslowadoseascanbeachieved,preferablynoneat
all.Aftertheglucocorticoidshavebeentapered,wethentrytotaperpyridostigmine.Many,butcertainlynotall,
patientscanbeminimallysymptomaticorinremissionononeimmunotherapyagentalone.
BridgetherapyForthosepatientswithMGinwhomitisespeciallydesirabletoavoidglucocorticoids(such
asthosewithpoorlycontrolleddiabetes)orforthosewhoarenotsuccessfullyweanedtolowerdosesof
prednisone,weoftenusemonthlycoursesofIVIGuntilthemoreslowlyactingimmunotherapytakeseffect.
MonthlyplasmapheresisisanalternativetoIVIG.However,venousaccessproblemsdevelopwithfrequentuseof
plasmapheresis,makingitlesspracticalthanIVIGforuseasabridgetherapy.
RefractorydiseaseThereisasmallcohortofpatientswithgeneralizedMGwhoarerefractoryto,orare
limitedbythespecifictoxicitiesof,thefirstlineimmunotherapies(eg,azathioprine,mycophenolate,or
cyclosporine).Somerequireunacceptablyhighdosesofglucocorticoidsdespiteconcurrentuseoftheseagents.In
theserefractorypatients,monthlyIVIGortheuseofrituximabisoftenbeneficial.(See"Chronicimmunomodulating
therapiesformyastheniagravis",sectionon'Rituximab'.)
NeedforthymectomyInparallelwithsymptomatictreatmentandimmunotherapeuticagentsforMG,we
considerthymectomybecauseofitspotentiallongertermbenefit.(See"Thymectomyformyastheniagravis".)
Patientswiththymomaclearlyneedsurgicaltreatment.However,theneedforthymectomyislesscertaininthose
withnonthymomatoustissue.Weadvisesuchpatientsthatthelikelihoodofmedicationfreeremissionisabout
twiceashighwiththymectomythanwithout,andthatthelikelihoodofbecomingasymptomaticisaboutoneanda
halftimesashighwiththymectomy[5].Wealsoemphasizethatthebenefitofthymectomyisdelayedandaccrues
overseveralyearspostoperatively.(See"Thymectomyformyastheniagravis",sectionon'Efficacy'.)
Weadvocatethymectomyassoonasthepatient'sdegreeofweaknessissufficientlycontrolledtopermitsurgery,
ifthepatientisamenabletothatsurgery.Wealsoprefertohavepatientsonrelativelylowdosesofglucocorticoids,
ifpossible,toavoidpostoperativeproblemswithwoundhealing.
Forpatientswithpreoperativebulbarorrespiratorysymptoms,wetrytodefersurgeryuntiltheyarereasonablywell
controlled.WeadministerIVIGorperformaseriesofplasmaexchangesoneortwoweeksbeforesurgery,ifthese
respiratoryorbulbarsymptomspersist.Theexacttimingofsurgeryandwhattechniquesareappropriateareissues
notsettled.
OcularmyastheniaTheelementsoftreatmentforocularmyastheniagravis(OMG)arethesameaswith
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generalizedMG.However,differencesinthesymptomatology,disability,andprognosisleadtosomedifferencesin
thetreatmentapproachforthesepatients.Thisisdiscussedinmoredetailseparately.(See"Ocularmyasthenia
gravis",sectionon'Treatment'.)
Age60andoverWedonotroutinelysuggestthymectomyinpatientsover60yearsofage,unlessathymoma
ispresent.(See"Thymectomyformyastheniagravis",sectionon'Patientageandseverityofdisease'and"Clinical
presentationandmanagementofthymomaandthymiccarcinoma".)
Althoughtherearenofirmdatatosupportastrictagelimitforthissurgicaltherapy,manyfeelthatthymectomyis
lesslikelytobebeneficialinthisagegroupduetothehighincidenceofthymicinvolutionandanincreased
operativeriskduetocomorbidities.Weuseage60asaroughruleofthumb,butthisismoderatedbythepatient's
overallhealth,functionalage,andthepatient'swishesafterreviewingtheissueswithhimorher.Despitethe
reluctanceatmanycenterstoperformthissurgeryonolderpatientswithMG,thereissomeevidencethatpatients
overage60maybenefitfromtheprocedure[28].
Otherthanatendencytouseglucocorticoidsmoresparinglyinthisgroup,theuseofpyridostigmine,azathioprine,
andmycophenolatemofetildoesnotdifferfromthatdetailedabove.Duetothepotentialrenalsideeffects,wedo
notcommonlyusecyclosporineinthesepatients.Therearefewstudiesthatlookatthetreatmentsinthis
particularagegroup.However,theusefulnessofimmunotherapyissupportedbyastudyofoutcomeatoneyearor
longerin149patientswithdiseaseonsetafterage60whoweretreatedwithazathioprinewithorwithoutprednisone
[29].Betteroutcomesandfewersideeffectswereobservedwhenprednisonewasavoidedorwascombinedwith
azathioprine.
ChildrenAswithadults,thetreatmentofchildrenwithMGshouldbeindividualizedbasedontheseverityand
paceofthedisease[8,9,30].Pyridostigmineisthefirstlineoftherapy(see'Pyridostigminedosing'above).If
anticholinesterasemedicationsarenotsufficient,plasmapheresisorintravenousimmuneglobulinmaybeused,but
thebenefitsaretransient.
Glucocorticoidsaregenerallylimitedtoseverediseasethatisunresponsivetotheseinterventions.Glucocorticoids
retardbonegrowth,increasetheriskofadultosteoporosis,andareespeciallyproblematicforchronicusein
children.Azathioprine,mycophenolatemofetil,andcyclosporinehavebeenusedsuccessfullyinjuvenileMG
[9,30],butconcernsaboutseriousadverseeffects,includingimpairedfertilityandthelatedevelopmentof
malignancy,areofevengreaterconcernthaninadults.
AsalongtermtreatmentforMG,thymectomyhasbeenperformedsuccessfullyandwithlowmorbidityinchildren
[31].ThymectomyisawidelyacceptedoptionforperipubertalandpostpubertalchildrenwithgeneralizedMGwho
havepositiveacetylcholinereceptorantibodiesorwhoareseronegative[8,9,3032].Theratesofimprovementand
remissionseeninuncontrolledseriesappeartobesimilartothatreportedinadultsafterthymectomy[31].
Thorascopicthymectomy,potentiallyamoreacceptabletreatmentinthisagegroup,hasbeenusedsuccessfullyin
asmallcaseseries[33].Thelikelihoodofimprovementorremissionafterasingleprocedure(thymectomy)
comparedwithlongtermimmunotherapymakesthisoptionareasonableconsiderationinallchildrenwhohave
morethanmilddisease.Nosignificantdeleteriousconsequencesofremovingthethymusinchildhoodhavebeen
reported[30].
SimilartoadultswithMuSKantibodypositiveMG(see"Thymectomyformyastheniagravis",sectionon'MuSK
antibodypositivemyasthenia'),childrenwithMuSKpositiveMGhavenotbeenshowntobenefitfromthymectomy.
Therefore,thymectomyisnotrecommendedforthisgroup.Theroleofthymectomyinprepubertalchildrenremains
controversial.Thisgrouphasahigherincidenceofspontaneousremissionandisalsomorelikelytobe
seronegative,makingconfirmationofthediagnosismoredifficult[8,30].
TheclinicaloutcomeinchildhoodMGvarieswithageofonset,race,andsex[34].Whitechildrenwithprepubertal
onsethavethebestprognosis.Thespontaneousremissionrateis44percentinthesechildren,andtheyrespond
welltoearlythymectomy.
PregnancyandtheneonatePregnancyhasavariableeffectonthecourseofMG.Itdoesnotworsenthelong
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termoutcome,buttheMGmayworsenduringthecourseofpregnancy.Thefirsttrimesterandthemonth
postpartumaretheperiodsofhighestriskofexacerbation.
Themanagementofmyastheniainpregnancyisdiscussedseparately.(See"Managementofmyastheniagravisin
pregnancy".)
TransientneonatalMGdevelopsin10to20percentofinfantsborntomyasthenicmothersduetotransplacental
passageofantiacetylcholinereceptorantibodies.Neonatalmyastheniaisdiscussedseparately.(See
"Neuromuscularjunctiondisordersinnewbornsandinfants".)
MyastheniccrisisMyastheniccrisisisalifethreateningcondition,anditischaracterizedbyneuromuscular
respiratoryfailure.Severebulbarweaknessthatproducesdysphagiaandaspirationoftencomplicatesthe
respiratoryfailure.Patientsinmyastheniccrisistypicallyexperienceincreasinggeneralizedweaknessasa
warning,althoughoccasionallyapatientwillpresentwithrespiratoryinsufficiencyoutofproportiontotheirlimbor
bulbarweakness.
Theevaluationandtreatmentofmyastheniccrisisisdiscussedseparately.(See"Myastheniccrisis".)
DrugsthatmayexacerbatemyastheniaSomemedicationsmaycauseasignificantincreaseinweaknessin
patientswithMG(table2).Theseincludeaminoglycosideantibiotics,betablockers,procainamide,quinidine,
quinine,andphenytoin[35].AnumberofotherdrugsmayunmaskorexacerbateMG,particularlythe
neuromuscularblockingagentsusedduringanesthesia,whichcanleadtoprolongedpostoperativeweaknessand
ventilatordependence.
Inaliteraturereviewofdruginducedmyasthenia,thedrugsthatweremostlikelytohaveanegativeimpactonMG
werethoseusedinthetreatmentofthedisease,including[36]:
Highdoseprednisone
Overuseofanticholinesterasedrugs
Anesthesiaandneuromuscularblockersforthymectomy
Aminoglycosiderelatedpostoperativerespiratorydepressioncausedthegreatestfrequencyofdruginduced
neuromuscularblockade.
Penicillamine,usedinotherautoimmunediseases,inducesanautoimmunemyasthenicsyndromeinapproximately
1percentofcases.ItsimulatesprimaryMGinthatitcaninduceocularorgeneralizedweaknesswiththe
productionofacetylcholinereceptorantibodies[37,38].Themyasthenicsymptomseventuallyresolveafterthe
penicillamineisdiscontinued.(See"Differentialdiagnosisofmyastheniagravis",sectionon'Penicillamineinduced
myasthenia'.)
ThefollowingdrugswarrantspecialconcerninpatientswithMG(table2):
Aminoglycosidesshouldbeavoidedandonlyusedifabsolutelynecessarywithclosemonitoring.
TelithromycinhasbeenassociatedwithexacerbationsorunmaskingofMGinseveralcasereports,often
withintwohoursofthefirstdose[39,40].Ablackboxwarninghasbeenaddedtothedruglabelstatingthat
telithromycinshouldnotbeusedinpatientswithMG.(See"Azithromycin,clarithromycin,andtelithromycin",
sectionon'Warningsabouttelithromycin'.)
Neuromuscularblockingagentsmaybenecessaryforanesthesiaorintubation,buttheirusedelays
emergencefromanesthesia,recoveryofmusclestrength,andweaningfrommechanicalventilation[41].
Thesedrugsshouldbejudiciouslytitratedifused.
Lidocaineandprocainemaycauseworseningifinjectedintravenously.
Magnesiumsulfateisrelativelycontraindicatedbecausemagnesiumhasasignificantinhibitoryeffecton
acetylcholinerelease.
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PenicillamineandinterferonalphashouldbeavoidedinpatientswithMGbecausetheycaninduceMG.
Fluoroquinoloneantibioticsshouldbeusedwithcaution.
Allbetablockersshouldbeusedwithcaution.
AllglucocorticoidsathighdosesmaycauseexacerbationofMGsymptomsduringearlystagesof
treatment.
Amonganticonvulsants,phenytoinandgabapentinhavebeenrarelyreportedtoexacerbateMG,butthese
drugsmaybeusedifneeded.Experimentalevidencesuggeststhatethosuximideandcarbamazepinemay
causeincreasedweakness,buttherearenoclinicalreports.
Centralnervoussystemdepressants,opioids,andmusclerelaxantsmayincreaseMGsymptomswhen
theseagentsareusedconcurrentlyorgiveninhighdoses.
StatintreatmentmaybeassociatedwithMG,assuggestedbyafewcasereportsandcaseseries[4246]
thatdescribeatotalof12patientswithneworworseningMGinthecontextofextensiveuseofthesedrugs.
ExacerbationofpreexistingMGwithinafewmonthsofstartingstatintherapywasreportedineightpatients
[4446],includingsixfromasinglecenterretrospectivestudyof170patientswithMGwhoweresurveyed
aboutstatintreatment[46].SymptomsofdenovoMGdevelopedwithinweeksofstartingstatinsinfour
patients[44,45].UnmaskingofsubclinicalMGduetostatinrelatedmyotoxicityappearedtobethemost
likelyexplanationforsomeofnewcases,andthecoincidentaloccurrenceofautoimmuneMGwithstatin
therapywasalsoaconsideration.
AgoodruleofthumbingeneralizedMGistoassumethatanymedicationmayexacerbateMGandtowatchfor
worseningfollowingtheintroductionofanewmedication.WhethertheassociationwithclinicalworseningofMGis
coincidentalorcasuallyrelatedmayrequirewithdrawalfromthemedicationandarechallenge.
ImmunizationsPatientswithgeneralizedMGwhodeveloprespiratoryinfectionsareatincreasedriskof
myasthenicexacerbationsandrespiratorycompromise[47].Thisincreasedriskmaybesharedbypatientswith
ocularMGofmorerecentonset(lessthanthreeyears),becausetheyarestillatriskofprogressingtogeneralized
disease.Incontrast,patientswithstableocularMGofthreeormoreyearsdurationaremuchlesslikelytodevelop
generalizeddiseaseandthereforearenotconsideredtobeatincreasedriskofmyasthenicexacerbationsor
respiratorycompromise.
Currentguidelinesrecommendannualseasonalinfluenzavaccinationforallindividualsreceiving
immunosuppressivetherapy,andforthosewithneurologicconditions,includingneuromusculardisorderssuchas
generalizedMG,orocularMGwithinthreeyearsofonset,thatcanpotentiallycompromisethehandlingof
respiratorysecretions.(See"Seasonalinfluenzavaccinationinadults"and"Seasonalinfluenzainchildren:
Preventionwithvaccines",sectionon'Indications'.)
Apopulationbasedstudysuggeststhattheinactivated(intramuscular)influenzavaccineissafeinadultswithMG
[48].Furthermore,inactivatedvaccines(eg,pneumococcalandintramuscularinfluenzavaccines)generallyare
consideredsafeinadultsorchildrenwithimmunocompromisingconditions,whilelivevaccinesgenerallyare
avoided.Thus,patientsbeingtreatedwithimmunotherapyforMGshouldnotreceivetheliveattenuated
(intranasal)influenzavaccine.
Thepneumococcalvaccineisrecommendedforallindividualswithchronicpulmonaryconditionsandforthose
receivingimmunosuppressivetherapy.WhileMGdoesnotusuallyresultinchronicpulmonarydisease,wesuggest
pneumococcalvaccinationforallindividualswithgeneralizedMG,andforthosewithocularMGwhoarewithin
threeyearsofonset,becauseoftheriskthatinfectionmaytriggeranMGexacerbationorcrisis.(See
"Pneumococcalvaccinationinadults"and"Pneumococcal(Streptococcuspneumoniae)conjugatevaccinesin
children".)
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INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsand
BeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyondthe
Basicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe
10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewith
somemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)
Basicstopic(see"Patientinformation:Myastheniagravis(TheBasics)")
SUMMARYANDRECOMMENDATIONS
ThefourbasictherapiesforMGincludesymptomatictreatments(anticholinesteraseagents),chronic
immunotherapies(glucocorticoidsandotherimmunosuppressivedrugs),rapidimmunotherapies(plasma
exchangeandintravenousimmuneglobulin[IVIG]),andthymectomy.Thetimeofonsetofclinicaleffectof
eachofthesetherapiesforMGvariesconsiderably(table1).(See'Overview'above.)
Werecommendtreatmentwithacetylcholinesteraseinhibitorsasthefirstlineoftreatmentforsymptomatic
MG(Grade1B).Pyridostigmineisthemostwidelyusedchoice.Foradultsandolderadolescents,atypical
startingdoseis30mgthreetimesaday.Forchildrenandyoungeradolescents,theinitialdoseis0.5to1
mg/kgeveryfourtosixhours.Thedoseofpyridostigmineisthentitratedbyitseffect.(See'Symptomatic
treatment'above.)
MostpatientswithMGwillneedsomeformofimmunotherapyinadditiontopyridostigmine.Werecommend
addingimmunotherapyforpatientswhoremainsignificantlysymptomaticonpyridostigmine,orwhobecome
symptomaticafteratemporaryresponsetopyridostigmine(Grade1B).Glucocorticoids,azathioprine,
mycophenolatemofetil,andcyclosporinearethemostwidelyused(see'Chronicimmunotherapies'above).
Thisapproachisdiscussedingreaterdetailseparately.(See"Chronicimmunomodulatingtherapiesfor
myastheniagravis".)
Plasmapheresis(withplasmaexchange)andIVIGworkquicklybuthaveashortdurationofaction.In
additiontotreatmentofmyastheniccrisis,theserapidtherapiesareusefulinpresurgicaltreatmentof
moderatetosevereMG.Theyarealsousedasa"bridge"wheninitiatingsloweractingimmunotherapies,
andasperiodicadjuvantstootherimmunotherapeuticmedicationsinrefractoryMG.(See'Rapid
immunotherapies'above.)
Wesuggestthymectomyforpatientswithoutthymomabelowage60yearswhohavegeneralizedMGand
eitherhaveAChRantibodies,orhavenodetectableAChRorMuSKantibodies(ie,seronegativeMG)(Grade
2C).WesuggestnotperformingthymectomyinpatientswithMuSKantibodyassociatedMGwithout
thymoma(Grade2C).(See'Generalizedmyasthenia'aboveand'Age60andover'aboveand"Thymectomy
formyastheniagravis".)
Attemptedsurgicalexcisionisthetreatmentofchoicefornonmetastaticthymomaandthymiccarcinoma.
(See"Clinicalpresentationandmanagementofthymomaandthymiccarcinoma",sectionon'Management'.)
AnumberofdrugscanunmaskorexacerbateMG(table2).Avoidanceofaminoglycosideantibiotics,
magnesiumsulfate,penicillamine,andinterferonalphainpatientswithMGisprudent.Likewise,beta
blockers,procainamide,quinidine,andquinineshouldbeavoidedwhenpossible.Cautioususeofdrugs
listedinthetable(table2),particularlytheneuromuscularblockingagents,isadvisedwheneverthereisa
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clearrequirementforanyoftheseagents.(See'Drugsthatmayexacerbatemyasthenia'above.)
ThetreatmentofMGishighlyindividualizedanddependsupontheageofthepatient,theseverityofthe
disease,andthepaceofprogression.TreatmentoptionsandsuggestionsforgeneralizedMG,ocularMG,
patientsover60,andchildrenarediscussedindetailabove.(See'Generalizedmyasthenia'aboveand
'Ocularmyasthenia'aboveand'Age60andover'aboveand'Children'above.)
ForallindividualswithgeneralizedMG,andthosewithocularMGwhoarewithinthreeyearsofonset,we
suggestpneumococcalvaccinationandannualintramuscular(inactivated)seasonalinfluenzavaccination
(Grade2C).PatientsbeingtreatedwithimmunotherapyforMGshouldnotreceivetheliveattenuated
(intranasal)influenzavaccine.(See'Immunizations'above.)
ThemanagementofMGinpregnancyisdiscussedseparately.(See"Managementofmyastheniagravisin
pregnancy".)
ThemanagementofrapidlyworseningMGandmyastheniccrisisisdiscussedseparately.(See"Myasthenic
crisis".)

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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42. ParmarB,FrancisPJ,RaggeNK.Statins,fibrates,andocularmyasthenia.Lancet2002360:717.
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Topic5157Version11.0

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GRAPHICS
Commonlyusedtherapiesformyastheniagravis

Timetoonsetof

Timetomaximal

effect*

effect*

Symptomatictherapy
Pyridostigmine

10to15minutes

2hours

Prednisone

2to3weeks

5to6months

Azathioprine

~12months

1to2years

Mycophenolatemofetil

6to12months

1to2years

Cyclosporineandtacrolimus

~6months

~12months

Plasmapheresis

1to7days

1to3weeks

Intravenousimmune
globulin

1to2weeks

1to3weeks

1to10years

1to10years

Chronicimmunotherapies

Rapidimmunotherapies

Surgery
Thymectomy

*Estimatedtimesareroughguidelinesbaseduponclinicalexperienceinmyastheniagravis.
Graphic70721Version4.0

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Drugsthatmayunmaskorexacerbatemyastheniagravis*
Anestheticagents

Antirheumaticdrugs

Chloroprocaine

Chloroquine

Diazepam

Penicillamine

Ether
Halothane
Ketamine

Cardiovasculardrugs
Betablockers
Bretylium

Lidocaine

Procainamide

Neuromuscularblockingagents

Propafenone

Propanidid

Quinidine

Procaine

Verapamilandcalciumchannelblockers

Antibiotics
Aminoglycosides
Amikacin
Gentamicin
Kanamycin
Neomycin
Netilmicin
Paromomycin

Glucocorticoids
Corticotropin
Methylprednisolone
Prednisone

Neuromuscularblockersand
musclerelaxants
Botulinumtoxin

Spectinomycin

Magnesiumsulfateandmagnesiumsalts

Streptomycin

Methocarbamol

Tobramycin

Fluoroquinolones
Ciprofloxacin
Gemifloxacin
Levofloxacin
Moxifloxacin
Norfloxacin
Ofloxacin

Others

Ophthalmologicdrugs
Betaxolol
Echothiophate
Timolol
Tropicamide
Proparacaine

Otherdrugs
Anticholinergics

Ampicillin

Carnitine

Azithromycin

Cholinesteraseinhibitors

Clarithromycin

Deferoxamine

Clindamycin
Colistin
Erythromycin
Lincomycin

Diuretics
Emetine(Ipecacsyrup)
Interferonalpha

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Quinine

Iodinatedcontrastagents

Telithromycin

Narcotics

Tetracyclines

Anticonvulsants
Gabapentin

Oralcontraceptives
Oxytocin

Phenytoin

Ritonavirandantiretroviralprotease
inhibitors

Trimethadione

Statins

Antipsychotics

Thyroxine

Chlorpromazine
Lithium
Phenothiazines
*Drugslistedhereshouldbeusedwithcautioninpatientswithmyastheniagravis.Aminoglycosides
shouldbeusedonlyifabsolutelynecessarywithclosemonitoring.Pleaserefertothetextforfurther
information.
Graphic62302Version6.0

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Disclosures
Disclosures:ShawnJBird,MDNothingtodisclose.JeremyMShefner,MD,PhDNothingtodisclose.IraNTargoff,MD
Consultant/AdvisoryBoards:OklahomaMedicalResearchFoundationClinicalImmunologyLaboratory(myositisantibodytesting).JohnF
Dashe,MD,PhDEmployeeofUpToDate,Inc.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthrougha
multilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.Appropriatelyreferenced
contentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.
Conflictofinterestpolicy

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